Renal immunocytochemical distribution and pharmacological properties of the dual angiotensin II/AVP receptor

Abstract We have recently characterized a novel angiotensin II/vasopressin (Ang II/AVP) dual receptor coupled to adenylate cyclase and responding with equal sensitivity to Ang II and AVP. To gain insight into putative renal physiological roles of the dual Ang II/AVP receptor, we determined its pharmacological binding properties and renal immunocytochemical distribution. The effective displacement of [ 3 H]AVP by [1-deamino-Val 14 ,d-Arg 8 ]-vasopressin (DVDAVP), a specific antidiuretic AVP analogue, supports a V 2 -type AVP receptor characteristic of the Ang II/AVP receptor. Displacement of 125 I–Ang II by losartan but not by PD 123319 defines the Ang II/AVP receptor as a novel AT 1 receptor isoform coupled to adenylate cyclase, in contrast to prototype Ca 2+ -mobilizing AT 1 receptors. Neither Ang II nor AVP displace each other, corroborating the predicted discrete binding domains for Ang II and AVP but presenting an enigma for the dissection of putative Ang II–and AVP-specific hierarchical roles of the dual Ang II/AVP receptor. The renal cytolocalization of the Ang II/AVP receptor to the outer medullary thick ascending limb tubules and inner medullary collecting ducts is consistent with the well-established AVP stimulation of sodium and water reabsorption in these tubules. These data suggest that the Ang II/AVP receptor might provide the molecular basis for the observed similar stimulatory effects of Ang II and AVP on renal tubular sodium and fluid reabsorption at physiological hormone concentrations.